CN114761517A - Long-afterglow luminescent organic microsphere, preparation method and application thereof - Google Patents
Long-afterglow luminescent organic microsphere, preparation method and application thereof Download PDFInfo
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- CN114761517A CN114761517A CN201980102723.3A CN201980102723A CN114761517A CN 114761517 A CN114761517 A CN 114761517A CN 201980102723 A CN201980102723 A CN 201980102723A CN 114761517 A CN114761517 A CN 114761517A
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Abstract
The invention relates to a long afterglow luminescent organic microsphere, which comprises A) at least one light absorbing agent, B) at least one luminescent agent, wherein the luminescent agent is a monomeric non-polymeric compound and has a molecular weight of less than 10000g mol‑1C) at least one photochemical buffering agent of the formula (I), and
D) a support medium for adsorbing components A) to C); wherein the light absorber and the light emitting agent are structurally different compounds, and the content of the carrier medium is divided into four groupsThe total mass of components A) to D) is from 30% to 99%, more preferably from 35% to 95% and most preferably from 40% to 90%. The organic microspheres according to the invention are particularly suitable for immunochromatographic detection techniques. In addition, the invention also relates to a test paper, a probe and a detection method for immunochromatography detection.
Description
The invention relates to a long-afterglow luminescent organic microsphere, a preparation method and application thereof, in particular to application of the long-afterglow luminescent organic microsphere in an immunochromatography detection technology.
Immunochromatography assay (ICA) or Lateral flow immunoassay (LFA) was first used to detect human chorionic gonadotropin, and with the development of labeling technology, has also been widely used in the fields of medical testing, environmental monitoring, food safety, and the like. The immunochromatographic detection technology effectively combines the chromatographic technology and the antigen-antibody immunoreaction technology. In the immunochromatography detection technology, an immunochromatography detection test strip is often used, which has a main structure in which a polyvinyl chloride base plate is used as a support, and a sample pad (such as a glass cellulose membrane), a binding pad (such as a glass cellulose membrane), a nitrocellulose membrane (NC membrane) and a water absorption pad are arranged on the polyvinyl chloride base plate. When the sample flows under the capillary action, the antigen is combined with the probe on the combining pad to form immune complexes, the immune complexes are enriched and trapped on the detecting line (T line) of the NC membrane as the liquid continues to flow, the probe without the immune complexes is trapped by the quality control line (C line), and finally the probe is interpreted by naked eyes or an instrument.
The immunochromatography detection test strip widely used at present mainly comprises a colloidal gold immunochromatography test strip and a fluorescence immunochromatography test strip. The traditional immunochromatography detection technology mainly takes colloidal gold as an output signal, and because the optical density of a colloidal gold probe is insufficient, the detection sensitivity is low, the quantification is difficult, and the requirement of clinical diagnosis cannot be met. Subsequently, fluorescent probes were developed for immunochromatographic detection, with fluorescent dye-based luminescent probes being most widely used. The fluorochrome is usually directly labeled on the antibody or the microsphere coated with the antibody, or embedded in the microsphere to modify the antibody, and the fluorochrome is excited by a light source such as ultraviolet light to emit light. However, during the detection of the luminescence signal, the spontaneous fluorescence signal interference exists in the sample such as blood, and the interference of the optical signal is also generated by the irradiation of the excitation light source, and these adverse factors seriously affect the accuracy and stability of the detection signal.
The long-afterglow luminescent material is a special luminescent material, which can emit light for a long time after the excitation light source is removed. In the prior art, the long-afterglow luminescent material usually has a luminescent life longer than one hundred milliseconds, and has important application value in the fields of biomedicine, life science and the like. At present, commercial long afterglow luminescent materials are inorganic long afterglow luminescent materials such as rare earth or transition metal doped aluminate, silicate, titanate or sulfide. The long-afterglow luminescent material is used as a signal indicating probe to be applied to immunochromatography detection, so that the interference of excitation light and background fluorescence can be avoided. For example, CN105929155A discloses a long afterglow-based immunochromatographic test strip and a detection method thereof, wherein an inorganic long afterglow luminescent material is used, so as to effectively eliminate interference signals and improve the detection sensitivity and the quantitative accuracy of an object to be detected.
These inorganic long persistence luminescent materials based on rare earth or transition metal doping are usually prepared by high temperature solid phase calcination. High temperature solid phase synthesis is the most common and effective production method of the materials, mainly because high temperature is favorable for obtaining better long afterglow luminescence property, and the luminescence property of inorganic long afterglow materials synthesized by other non-high temperature methods is obviously reduced and is difficult to obtain wide application. However, the high-temperature solid-phase reaction conditions are harsh and high in energy consumption, the morphology of the material is difficult to control to be uniform, and the particle size of the material is generally large. Although the material synthesized by the high-temperature solid-phase method can be further reduced in size by means of milling and screening, the emission luminance drastically decreases after the particle size is reduced to the nanometer level (for example, when the particle diameter is less than 1000 nm). For example, if commercial micron-sized inorganic long afterglow powders are ground to the order of 100nm, the luminescence brightness of the microspheres may be reduced by two orders of magnitude.
Therefore, the preparation of the inorganic long-afterglow luminescent microspheres is difficult at present, and the inorganic long-afterglow luminescent microspheres have weak luminescence, so that long-afterglow luminescent signals which are obviously visible to the naked eye are difficult to obtain. The detection of weak signals requires the aid of complex professional equipment, and the effectiveness is limited when applied to immunochromatography.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, the present invention provides a long-lasting luminescent organic microsphere with higher brightness and unaffected or even longer afterglow time.
Different from the inorganic long-afterglow luminescent material based on the photophysical process in the prior art, the long-afterglow luminescent material is based on an organic system, and the system introduces photochemical reaction between light energy input and light energy output by utilizing the characteristics of photochemical reaction to organically fuse photophysics and chemistry. In the long-afterglow luminescent material based on the organic system, the luminescent process can involve photochemical interaction among a plurality of chemical substances, wherein the input excitation light energy is finally released in a luminescent form through a series of photochemical energy conversion and metabolic processes, so that the long-afterglow luminescence is realized. Energy conversion and metabolic processes include energy input, energy buffering, energy extraction, energy transfer, and energy release. The original very rapid photon radiation transition process (nanosecond magnitude to microsecond magnitude) is changed through photochemical reaction, energy is slowly released and is finally emitted in the form of light energy, so that the ultra-long light-emitting time (millisecond magnitude to hour magnitude) is obtained, and the limitation of short light-emitting life of organic molecules is greatly improved.
Further, the inventors found that the long afterglow material based on organic system not only can obtain afterglow with longer time and higher brightness, but also some long afterglow luminescent organic materials are particularly suitable for preparing long afterglow luminescent microspheres without losing afterglow brightness and duration, thereby being particularly suitable for immunochromatography detection technology. Even in many cases, the afterglow luminance can be increased to a level visible to the naked eye or above, and the long afterglow luminescence signals can be collected and analyzed by common electronic equipment such as a mobile phone, so that the practicability of the material is greatly improved.
In this application, the term photochemical reaction is a series of chain reactions, including photochemical addition, photo-oxidation, photochemical dissociation, and bond breaking recombination.
In the present application, the terms "long afterglow luminescent organic microsphere", "long afterglow material" and "long afterglow microsphere" have the same meaning and are used interchangeably, unless otherwise specified.
Accordingly, in a first aspect, the present invention provides a long persistence luminescent organic microsphere comprising
A) At least one light-absorbing agent, which is,
B) at least one luminescent agent which is a monomeric, non-polymeric compound and has a molecular weight of less than 10000g mol -1，
C) At least one photochemical buffer agent of formula (I),
wherein formula (I) is described in detail below, and
D) a support medium for adsorbing components A) to C);
wherein the light absorber and the light emitter are structurally different compounds and the content of the carrier medium is from 30% to 99%, more preferably from 35% to 95% and most preferably from 40% to 90% based on the total mass of the four components A) to D).
Preferably, the long persistent luminescent organic nanoparticles consist of components a) to D).
In a second aspect, the invention provides a probe comprising the long-afterglow luminescent organic microsphere.
In a third aspect, the invention provides a method for preparing the long-afterglow luminescent organic microsphere.
In a fourth aspect, the present invention provides a method for preparing a probe comprising the long-lasting luminescent organic microsphere.
In a fifth aspect, the present invention provides a test strip for immunochromatographic assay.
In a sixth aspect, the invention provides a method for immunochromatography detection by using the long-afterglow luminescent organic microspheres.
Other aspects of the invention are presented in the other independent and dependent claims.
Besides the advantages, the components of the long-afterglow luminescent microsphere are flexibly prepared, the composition and the properties of the material can be designed according to actual requirements, flexible and various nanostructures can be obtained, and the microsphere has tailorable luminescent performance. The wavelength of the energy-charging excitation light and the wavelength of the long afterglow luminescence can be respectively adjusted, and the combination scheme of the light absorbing agent and the light emitting agent can be conveniently adjusted and replaced, so that the long afterglow luminescence with rich colors can be efficiently realized.
Preferably, the long afterglow luminescent nano materials according to the present invention do not contain or contain very little inorganic long afterglow constituents such as SrAl2O 4:Eu 2+,Dy 3+For example not more than 0.1% by weight, based on the material mixture.
The grain diameter of the long afterglow luminescent microsphere can reach 5nm to 1000nm, more preferably 50nm to 800nm, and the most preferably nanometer grain diameter is 100nm to 500 nm. In the context of the present invention, the morphology and particle size of all particles of the microspheres can be characterized by taking images by electron microscopy and recording the average diameter of the microspheres from multiple measurements as the particle size. Methods for the characterization of such microspheres are known to the skilled person and can be measured, for example, using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) instruments.
Under the same test conditions, the luminous intensity of the long-afterglow luminous organic microsphere can far exceed the nanoscale commercial inorganic long-afterglow material SrAl2O 4:Eu 2+,Dy 3+The level of (c). In particular, the long-afterglow luminescent organic microspheres can continuously emit light after the excitation light is turned off, and the long-afterglow luminescent time can reach 100ms to 3600s, preferably 500ms to 1200s, more preferably 1s to 600s, and most preferably 2s to 60 s. The long afterglow luminance of the long afterglow material can reach 0.1mcd m -2–10000mcd m -2Preferably at 0.32mcd m-2–8000mcd m -2More preferably at 1mcd m-2–5000mcd m -2. Based on the properties, the long-afterglow microsphere can provide a complete material basis for an immunochromatography detection technology.
In addition, the long-afterglow microsphere can be used for preparing an immunochromatographic nanoprobe with high afterglow brightness, and a test strip for immunochromatographic detection with high stability, good repeatability and high sensitivity can be obtained. The detection objects comprise mycotoxin, pathogenic bacteria, viruses, inflammatory factors, tumor markers and the like.
Light absorber and luminophore
In the present application, light absorbers and light emitters are known per se from the prior art. A light absorber generally refers to a substance that absorbs and captures light energy from a natural or artificial light source. The light absorber can be selected from a range including conventional photosensitizing agents and other energy donor materials. And a luminescent agent generally refers to a substance that is capable of ultimately emitting energy in the form of light energy. The light-emitting agent may be a light-emitting substance that can generate fluorescence, phosphorescence, or the like. Relevant light-emitting molecular groups are known per se and reference may be made, for example, to the reviewed article Nature Methods,2005,2, 910-.
In order to achieve the beneficial effects of the long afterglow materials of the present invention, in particular, for example, improvement of afterglow intensity and time, a clear distinction is made between the two components of the luminescent agent and the light absorbing agent in the compositions of the present invention, so that each component plays a role of absorbing light energy and releasing light energy, respectively, thereby achieving energy utilization paths of energy input, energy buffering and energy output after combination with the specially screened photochemical buffering agent. This also means that, in an advantageous embodiment, a compound which has both a light-absorbing group and a light-emitting group in its structure so that both functions can be performed in the same molecule is not a light-emitting agent or a light-absorbing agent according to the invention and does not give the excellent technical effects of the invention either. On one hand, if the compound is equivalent to packing and binding the light absorbent and the luminescent agent together with the properties of the light absorbent and the luminescent agent, the excitation and the luminescence properties of the long-afterglow material cannot be adjusted respectively, for example, when one compound is selected according to the requirement of actual excitation and energy charging, the luminescence property of the material is fixed at the same time, and vice versa; on the other hand, such a compound is equivalent to fixing the ratio of the light absorber to the luminescent agent to, for example, 1:1, and cannot adjust both the intensity of the light absorption degree and the level of the luminescence level; moreover, the number of materials having both the efficient light absorption function and the efficient light emission function is relatively small, which limits the variety of the long afterglow materials.
In the long afterglow luminescent material according to the present invention, the selection of the light absorbing agent and the luminescent agent has certain regulation standards. In general, compounds having a relatively large molar absorptivity are selected as light absorbers, such as photosensitizers or energy donor dyes; while compounds with higher luminescence quantum efficiencies are selected as luminescent agents, for example luminescent dyes. In addition, the absorption peak of the light absorbent should overlap the emission peak of the light emitting agent as little as possible to avoid the adverse effect of the long afterglow luminescence being attenuated by the absorption of the absorbent.
The inventors of the present application have found that in the long persistence light-emitting organic microsphere according to the present invention, particularly in the aspect of immunochromatography detection technique, from the viewpoint of enhancing the light-emitting luminance or the intensity of the light-emitting signal, the light-absorbing agent and the light-emitting agent should be advantageously different molecular formulae selected fromOr at least one compound of different structure: porphyrin and phthalocyanine dyes, metal complexes, acene compounds, BODIPY compounds, Quantum Dots (QDs), graphene, and derivatives or copolymers of these compounds. However, advantageously, the luminophores used in the present invention are monomeric, non-polymeric compounds and have a molecular weight of less than 10000g mol -1. In the context of the present application, the molecular weight refers to the weight average molecular weight of the compound, which can be determined by means of mass spectrometry, gas chromatography, liquid chromatography. An alternative instrument may be, for example, a mass spectrometer, or a liquid-mass spectrometer. Herein, the non-polymeric compound means that the compound structure does not include more than 2 repeating units obtained by polymerization or oligomerization.
More advantageously, particularly from the viewpoint of immunochromatographic detection techniques, the light-absorbing agent and the light-emitting agent preferably used for the long-afterglow organic microspheres of the present invention are each selected from the following.
(1) Light absorber
Preferably, the light absorber may be selected from the group consisting of porphyrins and phthalocyanines, transition metal complexes, Quantum Dots (QDs), and derivatives or copolymers of these compounds. These compounds are known per se to the person skilled in the art, some non-limiting examples of light absorbers being mentioned below.
As porphyrin-based dyes and complexes thereof, mention may be made, for example, of the following compounds:
as phthalocyanine type dyes and complexes thereof, for example, the following may be mentioned:
in the structural formulae of these light absorber compounds shown above,
x represents a halogen such as F, Cl, Br, I; and
M ═ metal elements such as Al, Pd, Pt, Zn, Ga, Ge, Cu, Fe, Co, Ru, Re, Os, and the like.
Each substituent R is as R1-24Represents H, hydroxyl, carboxyl, amino, mercapto, ester, aldehyde, nitro, sulfonic acid, halogen, or alkyl, alkenyl, alkynyl, aryl, heteroaryl with N, O or S, alkoxy, alkylamino having 1 to 50, preferably 1 to 24, e.g. 2 to 14 carbon atoms, or combinations thereof. Preferably, the above-mentioned group R is R1-24Each independently selected from methoxy, ethoxy, dimethylamino, diethylamino, methyl, ethyl, propyl, butyl, tert-butyl, phenyl or combinations thereof.
Transition metal complexes which can be used as light absorbers are known per se, and are preferably complexes of porphyrins and phthalocyanines dyes as those shown above.
Suitable quantum dot materials include, for example, graphene quantum dots, carbon quantum dots, and heavy metal quantum dots.
Heavy metal quantum dots include, for example, Ag2S, CdS, CdSe, PbS, CuInS, CuInSe, CuInGaS, CuInGaSe and InP quantum dots. The outer layer can be coated with shell layer of Ag to form core-shell structure2One or more of S, CdS, CdSe, PbS, CuInS, CuInSe, CuInGaS and CuInGaSe, or ZnS layer.
Preferably, the quantum dots are modified with surface ligands, which may be, for example, oleic acid, oleylamine, octadecene, octadecylamine, n-dodecyl mercaptan, combinations thereof, and the like. In some more advantageous cases, the ligands on the surface of the quantum dots are partially exchanged by a ligand exchange strategy for molecular structures containing triplets, such as carboxyanthracene, carboxytetracene, carboxypentacene, aminoanthracene, aminotetracene, aminopentacene, mercaptoanthracene, mercaptotetracene, mercaptopentacene, and the like.
In a more preferred embodiment, the light absorbers are preferably selected from complexes of porphyrins and phthalocyanines, Quantum Dots (QDs), and derivatives of these compounds. Such as one or more of the following exemplary compounds:
and quantum dot materials such as graphene quantum dots, CdSe quantum dots and PbS quantum dots.
(2) Luminescent agent
Preferably, the luminescent agent may be selected from iridium complexes, rare earth complexes, acene-based compounds, BODIPY-based compounds, and derivatives and copolymers of these compounds.
As the BODIPY-based compound, for example, the following compounds can be mentioned:
as the acene-based compounds, there may be mentioned, for example, the following compounds:
In the structural formulae of these luminescent agent compounds shown above,
n is an integer of 0 or more, for example, 0, 1, 2, and 3;
each substituent R is as R1-16Represents H, hydroxyl, carboxyl, amino, mercapto, ester, aldehyde, nitro, sulfonic acid, halogen, or alkyl, alkenyl, alkynyl, aryl, heteroaryl with N, O or S, alkoxy, alkylamino having 1 to 50, preferably 1 to 24, e.g. 2 to 14 carbon atoms, or combinations thereof. Preferably the group R is as R1-16Selected from methoxy, ethoxy, dimethylamino, diethylamino, methyl, ethyl, propyl, butyl, tert-butyl, phenyl; or a combination thereof.
In iridium complexes suitable as luminescent reagent, the composition of the ligand may be a combination of one or more different ligands, the schematic structure of which and the type of a part of the C-N, N-N, O-O and O-N ligands are exemplarily shown below (the C-N, N-N, O-O and O-N ligands shown therein are schematic structures thereof and are respectively highlighted by the coordination of the iridium atom Ir with the C and N atoms, two O atoms and O and N atoms in the ligand, such representation being familiar and understood to those skilled in the art):
Wherein the C-N ligand may have, for example, the following structure:
the O — N ligand may have, for example, the following structure:
the N-N ligand may have, for example, the following structure:
the rare earth complex as a luminescent agent may be, for example, a structure in which the central atom is a lanthanoid, the ligand is coordinated with the central atom with O or N, and the central atom is generally Eu, Tb, Sm, Yb, Nd, Dy, Er, Ho, Pr, or the like. These rare earth complexes have a coordination number of about 3 to 12, preferably 6 to 10. In actual rare earth complexes, the ligand species, number of each ligand, and total coordination number may vary. Reference is made, for example, to the review article coord chem. rev.,2015,293-294,19-47 by Jean-Claude G.B u nzli.
In a more preferred embodiment, the luminescent agent is selected from the group consisting of iridium complexes, rare earth complexes, BODIPY compounds, perylene, and derivatives of these compounds. Such as one or more of these exemplary compounds:
photochemical buffer agent
In the long persistence luminescent materials according to the present invention, a photochemical buffer is important. The photochemical buffering agent mainly has the function of photochemical energy conversion, and different from a luminescent agent with the main function of luminescence, the buffering agent molecules do not emit light or emit light very weakly, and the molecular structure of the buffering agent does not generally comprise a group or a conjugated structure which can directly emit light. In particular, the photochemical buffering agents according to the invention are distinguished in kind from luminescent or light-absorbing agents, in particular those luminescent or light-absorbing agent substances listed in the invention. The photochemical buffering agent can assist in participating in photochemical reaction, and a bridge for energy exchange and storage is constructed between the luminous agent and the light absorbent. The energy extraction process of transition between energy levels is activated through a reaction step of addition, rearrangement or bond breaking in a photochemical reaction.
The photochemical buffering agents according to the invention are non-polymeric small-molecule compounds with a molecular weight of preferably less than 2000g mol-1More preferably less than 1000g mol-1. Likewise, the non-polymeric compound means that the structure of the buffer compound does not contain more than 2 repeating units obtained by polymerization or oligomerization.
In particular, the inventors have found that certain buffer compounds are particularly suitable for preparing microspheres with stable and good long-lasting luminescence properties. The buffer agent suitable for the long-afterglow luminescent microsphere is selected from the following structural formula (I):
wherein, the first and the second end of the pipe are connected with each other,
g and T are heteroatoms selected from O, S, Se and N;
R 1' and R2' and R4' to R8' are each independently selected from H, hydroxyl, carboxyl, amino, mercapto, ester, nitro, sulfonic, halogen, amide, or alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, aryl, aralkyl, heteroaryl or heteroaralkyl having N, O or S, or combinations thereof, having 1 to 50, preferably 1 to 24, carbon atoms, such as 2 to 14, wherein the aryl, aralkyl, heteroaryl or heteroaralkyl optionally has one or more substituents L; and
l is selected from hydroxyl, carboxyl, amino, thiol, ester, nitro, sulfonic, halogen, amide, or alkyl, alkenyl, alkynyl, alkoxy, and alkylamino groups having 1 to 50, preferably 1 to 24, such as 2 to 14, or 6 to 12 carbon atoms, or combinations thereof; and
R 3' is an electron withdrawing group or an aryl group comprising an electron withdrawing group.
In the context of this application, "aryl" means a group or ring formed by an aromatic compound as distinguished from an aliphatic compound, which is directly linked to another structural group or fused to another ring structure by one or more single bonds, and is thus distinguished from a group linked to another structural group by a spacer such as an alkylene or ester group, for example, an "aralkyl" or "aryloxy" or "arylester group". Similarly, they may be viewed as groups formed by replacing a ring carbon atom of an aryl group with a heteroatom N, S, Se or O, or replacing a carbon atom of an aliphatic ring such as a cyclic olefin with said heteroatom. Furthermore, unless indicated to the contrary, the term "aryl" or "heteroaryl" also includes aryl or heteroaryl groups substituted or fused with aryl, heteroaryl groups, such as biphenyl, phenylthienyl or benzothiazolyl groups. In addition, the "aryl" or "heteroaryl" may also include groups formed from aromatic or heteroaromatic compounds having functional groups such as ether groups or carbonyl groups, such as anthrone, diphenyl ether, or thiazolone, and the like. Advantageously, the "aryl" or "heteroaryl" according to the invention has 4 to 30, more preferably 5 to 24, for example 6 to 14 or 6 to 10 carbon atoms. The term "fused" means that the two aromatic rings have a common edge.
In the context of the present application, the terms "alkyl", "alkoxy" or "alkylthio" refer to a straight-chain, branched or cyclic, saturated aliphatic hydrocarbon radical which is linked to other radicals by a single bond, an oxy or a thio radical, and which preferably has from 1 to 50, more preferably from 1 to 24, for example from 1 to 18, carbon atoms. The term "alkenyl" or "alkynyl" refers to a straight, branched or cyclic unsaturated aliphatic hydrocarbon group having one or more C-C double or triple bonds, preferably having from 2 to 50, more preferably from 2 to 24, such as from 4 to 18 carbon atoms.
In the context of this application, the term "alkylamino" refers to one or more alkyl-substituted amino groups, including monoalkylamino or dialkylamino groups, such as methylamino, dimethylamino, diethylamino, dibutylamino and the like.
In the context of the present application, the term "halogen" includes fluorine, chlorine, bromine and iodine, preferably fluorine.
In the context of the present application, the term "electron-withdrawing group" is understood to mean a group which, when it substitutes a hydrogen on an aromatic or heteroaromatic ring, results in a reduction in the density of the electron cloud on the ring. Such groups are widely known in the chemical arts. Preferably, in the present invention, the electron withdrawing group is selected from nitro, halogen, haloalkyl, sulfonic acid, cyano, acyl, carboxyl and/or combinations thereof.
Furthermore, in the context of the present application, the substituents listed in the definitions of the individual substituents can combine with one another to form new substituents in accordance with the principle of valency, which means, for example, C1-C6 alkyl estervinylenes (C1-C6 alkyl estervinylenes) formed by alkyl, ester and vinyl groups combining with one another1-6alkyl-O-C (═ O) -C ═ C-) is also in the definition of the relevant substituents.
In a preferred embodiment, the ring portion
Can be selected from
More preferably, G and T are selected from S and O, most preferably one of G and T is S and the other is O.
In a preferred embodiment, R1' and R2' and R4' to R8' are each independently selected from alkyl, alkoxy, alkylamino or aryl groups having 1 to 18, preferably 1 to 12, more preferably 1 to 16 carbon atoms, or combinations thereof, wherein said aryl groups may be substituted or unsubstituted with one or more groups L and are preferably phenyl substituted or unsubstituted with one or more groups L.
Preferably, L is selected from hydroxyl, sulfonic acid, halogen, nitro, straight or branched alkyl having 1 to 12, more preferably 1 to 6 carbon atoms, alkoxy, alkylamino, amino, or combinations thereof.
More preferably, the group R1' and R2' and R4' to R 8' is selected from methoxy, ethoxy, dimethylamino, diethylamino, dibutylamino, methyl, ethyl, propyl, butyl, tert-butyl, or a combination thereof.
More preferably, the group R3' is selected from an electron withdrawing group or an aryl group comprising an electron withdrawing group, preferably selected from nitro, cyano, halogen, haloalkyl and/or combinations thereof. Accordingly, the aryl group containing an electron withdrawing group preferably includes an aryl group having one or more substituents selected from nitro, cyano, halogen and/or haloalkyl on the ring, preferably a phenyl group such as a fluorophenyl group or a perfluorophenyl group.
In a particularly preferred embodiment, the photochemical buffering agent is selected from compounds such as:
carrier medium
The long-afterglow organic microsphere of the invention must contain a component D) carrier medium in addition to the component A) light absorber, the component B) luminescent agent and the component C) photochemical buffering agent. Optionally, other processing aids for microsphere preparation or components to further improve the long-lasting glow-emitting effect may be included in addition to these.
According to the invention, the support medium serves to adsorb the particular components A) to C) described above and to facilitate the formation of stable microspheres supporting components A) to C). The inventors of the present application found that the long persistence organic microspheres of the present invention are particularly suitable for satisfying the above requirements, and particularly suitable for the immunochromatography detection technique to prepare the detection test paper, the carrier medium is selected from one or more of styrene polymer microspheres, protein nanomedia and silica microspheres, and more preferably protein-forming nanomedia and styrene polymer microspheres. The silicon microspheres refer to silicon dioxide microspheres. The styrene polymer microspheres include homopolymers of styrene or copolymers thereof with other copolymerizable monomers, such as alkenes, alkynes, or unsaturated carboxylic acids or anhydrides or esters thereof, such as butadiene, maleic anhydride, or (meth) acrylic acid. Silica microspheres and styrene polymer microspheres are known and commercialized in the art, and large-scale microspheres having a uniform particle size can be synthesized by a known method. The protein used to form the protein nanomedia is not particularly limited in theory, but is preferably selected from one or more of Bovine Serum Albumin (BSA), Human Serum Albumin (HSA), silk fibroin, and casein, and more preferably bovine serum albumin. Methods of forming microspheres from these proteins are also known in the art. Furthermore, it may be preferred to make these support matrix surfaces contain groups such as amino, carboxyl, and/or aldehyde groups, so that the microsphere surfaces of the present invention may be coupled with antibodies or aptamers capable of immunoreacting with a particular antigen using these groups.
Within the scope of the present invention, the skilled person will appreciate that the morphology of the long persistence microspheres of the present invention will in fact depend on the structural morphology of the carrier medium or the processing technique. Thus, it may be advantageous to directly mix a carrier medium that is itself microspheroidal, such as silica microspheres, with other components to form long-lasting microspheres, or to mix a carrier medium that is non-spherical, such as protein nanocarrier media, with other components, and then form long-lasting microspheres by known microsphere formation processes (as shown in the examples). The microspheroidal support medium may comprise a microspheroidal structure as follows: core-shell structures, oil-in-water structures, water-in-oil structures, mesoporous structures, hollow structures, swellable structures, and the like. Generally, as the particle size of the long-afterglow organic microspheres increases, the number or the mass of the components A), B) and C) contained in a single microsphere increases, so that the long-afterglow luminescence enhancement of the single microsphere is beneficial to the high-efficiency detection of a test signal in the immunochromatography process; however, too large a particle size is not favorable for lateral chromatography of the microspheres on a test strip. Therefore, in order to obtain a desired immunochromatographic detection effect, the long-lasting luminescent organic microspheres of the present invention advantageously have a particle size in the range of 5nm to 1000nm, more preferably 50nm to 800nm, most preferably 100nm to 500 nm.
In an advantageous embodiment, the support medium D) is preferably present in an amount of from 30 to 98%, more preferably from 35 to 95%, most preferably from 40 to 90%, for example from 50 to 80%, based on the total mass of the four components a) to D). When the content of the component D) is too high, the luminance of the long-afterglow luminescence decreases, so that effective immunoassay based on the long-afterglow luminescence signal cannot be performed. When the content of the component D is too low, the formed microspheres have poor dispersibility and stability, and even the material cannot form a nano structure, so that the application requirement of immunoassay cannot be met.
In addition, in the long afterglow material composition according to the present invention, adjusting the molar ratio of the light absorber to the luminescent agent within an appropriate range can further improve the effect of long afterglow. In an advantageous embodiment, the molar ratio of light absorber to luminescent agent is in the range of 1:2 to 1:10000, preferably 1:10 to 1:8000 or 1:50 to 1:6000, more preferably 1:100 to 1:4000 or 1:200 to 1: 2000. In an advantageous embodiment, the photochemical buffer may be present in an amount of from 0.1% to 80%, preferably from 0.3% to 60%, more preferably from 0.5% to 40%, most preferably from 1% to 20%, based on the total mass of the three components A) to C) of the material.
When the proportion of the light absorber is too high, there is a disadvantage that the long afterglow luminescence is attenuated by the absorption of the light absorber. When the proportion of the light absorber is too low, the absorbed excitation light energy is relatively limited, and the long afterglow luminescence is also weak. In addition, when the photochemical buffering agent is too small, the energy buffering capacity is weak, so that the performance of the long-afterglow luminescence is adversely affected, for example, the stability and the luminescence brightness of the long-afterglow luminescence are affected. When too much buffering agent is added in the system, collision energy transfer among all components is hindered, and the buffered energy cannot be effectively transmitted out and is dissipated, so that the long-afterglow luminescent performance is reduced.
The long afterglow material can be directly processed from solution to prepare the long afterglow luminescent organic microsphere, thereby being conveniently applied to the field of immunochromatography test strip detection.
The excitation and emission wavelengths of the long afterglow luminescent material system are easy to regulate and control, and the long afterglow luminescent material can cover purple, blue, green, yellow, red and near infrared spectral regions. By selecting the type of light absorber or light emitter and appropriate structural modification as necessary, the operable range of excitation and emission is very wide, so that the combination of actual excitation and emission properties is very rich. Preferably, the adjustable range of the wavelength of the excitation light is 300nm to 1000 nm. In addition, the long afterglow luminescence may be luminescence based on an up-conversion mechanism, luminescence based on a down-conversion mechanism, or luminescence with zero stokes shift. When the light with the wave band of lambda 1 is used for excitation, the wave band of the emitted light of the long afterglow luminescence lambda 2 is flexibly distributed, and the long afterglow luminescence can cover all the wave bands of ultraviolet visible near infrared. When the lambda 1 is less than the lambda 2, the light with the shorter wavelength is excited to realize the light emission with the longer wavelength, namely the wavelength of the excitation light is red-shifted than that of the emission light, and the light emitting device belongs to a conventional down-conversion light emitting mode; when the lambda 1 is more than lambda 2, the light with the longer wavelength is excited to realize the light emission with the shorter wavelength, namely the wavelength of the excitation light is blue-shifted than that of the emission light, and the light emission belongs to an up-conversion light emitting mode; when λ 1 is λ 2, i.e. the excitation light wavelength is in the same band as the emission light wavelength, it belongs to the light emission mode with zero stokes shift.
Various light sources may be used to energize the long persistence luminescent materials of the present invention. Common light source lighting equipment, point light sources, annular light sources and indoor and outdoor natural illumination can excite and charge the long afterglow luminescent agent system based on a photochemical mechanism. In a preferred embodiment, the light sources include solid-state lasers, gas lasers, semiconductor lasers, photodiodes, D65 standard light sources, organic light emitting diodes, ultraviolet lamps, flashlights, xenon lamps, sodium lamps, mercury lamps, tungsten filament lamps, incandescent lamps, fluorescent lamps, and natural sunlight, and combinations thereof. In a more preferable scheme, a laser and a light emitting diode are used as excitation light sources, the monochromaticity and the brightness of output light of the light sources are high, the energy charging can be selectively and rapidly excited, and in practical application, the light emitted by the light sources can be focused, divergent, annular and collimated light beams. The light output intensity of the excitation light source can have a wide range of power densities (1 μ W cm)-2–1000W cm -2) The excitation time also has a wide dynamic range (1 mus-1 h). In addition, the excitation light output by the light source may be continuous light, pulsed light, or an output mode of a combined mode, where the pulsed light is modulatable and has a wide modulation frequency range (0.001 Hz-100 KHz). In an advantageous embodiment, the required excitation time of the ultra-bright long-afterglow luminescent material according to the invention is short, and the irradiation time of the excitation light is 0.1s to 100s, preferably 0.5s to 60s, more preferably 1s to 30s, and most preferably 2s to 10 s.
In a second aspect, the present invention relates to a probe comprising the above long persistence luminescent organic microsphere. The probe comprises the long afterglow luminescent organic microsphere and the antibody or the aptamer loaded or coupled on the long afterglow luminescent organic microsphere.
In an advantageous embodiment, the antibody or aptamer is preferably present in the probe in an amount of 1% to 20%, more preferably 2% to 15%, and most preferably 5% to 12% by mass of the entire probe.
Suitable antibodies or aptamers are not, in theory, particularly limited. Preferably they are capable of specific immunological binding to an antigen of interest to be detected, including mycotoxins, pathogenic bacteria, viruses, inflammatory factors or tumour markers, preferably selected from C-reactive protein (CRP) antibodies, serum amyloid (SAA) antibodies, Procalcitonin (PCT) antibodies, alpha-fetoprotein (AFP) antibodies, carcinoembryonic antigen (CEA) antibodies, Prostate Specific Antigen (PSA) antibodies, cardiac troponin (CTn-I) antibodies and/or oligonucleotide fragments.
In a third aspect, the present invention relates to a method for preparing the long afterglow luminescent organic microsphere, which comprises the following steps:
(1) providing components A) to C); and
(2) the components A) to C) are dispersed and adsorbed onto the support medium component D) in a dispersion or solution.
Here, it may be advantageous to first mix the components a) to C) with one another and then disperse or dissolve them in a suitable solvent, or to disperse or dissolve the components a) to C) in succession in a suitable solvent, to form a solution. Suitable solvents are not particularly limited as long as they form a stable solution or dispersion, and may be, for example, liquid paraffin, a mixture of phenethyl alcohol-ethylene glycol and water, a mixture of mesitylene and ethanol, tetrahydrofuran, dichloromethane, or the like.
After the solution or dispersion comprising components a) to C) is obtained, the support medium microspheres or a solution or dispersion thereof may be added thereto. Alternatively, the solution or dispersion comprising components a) to C) may also be added to the solution or dispersion comprising microspheres of the support medium. The carrier medium may be dispersed with water or other suitable solvent, such as deionized water, Phosphate Buffered Saline (PBS), Borate Buffered Saline (BBS), and the like.
In the preparation of the solution or dispersion, if necessary, an auxiliary device such as an ultrasonic wave, a high-pressure homogenizer, or the like may be used, or appropriate heating may be performed with stirring.
After the stable dispersion of the long-lasting luminescent organic microspheres comprising the components A) to D) is obtained in the step (2), the stable dispersion can be directly utilized for subsequent use without treatment as required, such as for preparing test paper suitable for immunoassay. Alternatively, an antibody or aptamer may be further adsorbed or modified on the resulting microsphere, thereby obtaining a probe according to the present invention.
The preparation of the probes is known per se or can be obtained by a person skilled in the art with slight modifications according to known techniques. The preparation method mainly comprises the step of carrying out biological coupling on the long-afterglow luminescent microspheres and the antibody or the aptamer through functional reactive groups such as carboxyl, amino and aldehyde groups. For example, the coupling may be formed by a carboxyl-amino reaction or an aldehyde-amino reaction. Generally, the corresponding coupling method is selected according to the condition of the functional groups on the surface of the microsphere.
Accordingly, a fourth aspect of the present invention relates to a method for producing the probe as described above.
In a fifth aspect, the present invention provides a test strip for immunochromatography detection comprising the long-lasting luminescent organic microsphere or the probe as described above. The test paper comprises a sample pad, a combination pad, a test line and a quality control line, wherein the long afterglow luminescent organic microsphere or the probe is arranged on the combination pad.
The structure of test strips used in immunochromatographic detection techniques is known per se. The bonding pad, the test line and the quality control line can be attached to a base plate, such as a PVC base plate. For the structure of such a test strip, reference may be made to, for example, patent document CN105929155A, which is disclosed herein and incorporated herein in its entirety.
In one exemplary structure as shown in fig. 3, the test paper comprises a PVC base plate 1, a sample pad 2, a binding pad 3, a nitrocellulose membrane 4 and a water absorbent pad 5 are sequentially disposed on the base plate 1, wherein a test line 6 and a quality control line 7 are sequentially disposed on the nitrocellulose membrane 4 along a direction from the sample pad 2 to the water absorbent pad 5.
The immunochromatography technology mainly comprises double-antibody sandwich and competition method. The double-antibody sandwich method is mainly used for detecting macromolecular substances such as proteins and the like, such as tumor markers, viruses, inflammatory factors and the like. These detection methods are known per se. In an exemplary embodiment, the method uses a pair of paired antibodies directed to different epitopes of antigen, the capture antibody is fixed on the T line of NC membrane, the detection antibody coupling modified nano-probe is fixed on the binding pad, and the secondary goat-anti-mouse (or donkey-anti-mouse, goat-anti-rabbit, rabbit-anti-mouse, etc.) antibody is fixed on the C line of NC membrane as quality control line. In the detection process, a sample is dripped on the sample pad, the sample flows from left to right through capillary action and sequentially passes through the combination pad, and the T line and the C line generate specific immunoreaction. The competition method is mainly used for detecting the small molecular substances. In the method, for example, a whole antigen (a coupling product of a small molecule and a macromolecule) can be fixed on an NC membrane to form a T line, an antibody coupling modified nano probe is fixed on a binding pad, and a goat anti-mouse (or donkey anti-mouse, goat anti-rabbit, rabbit anti-mouse and the like) secondary antibody is used as a C line. In the detection process, a sample is dripped on the sample pad and sequentially passes through the combination pad, the T line and the C line through capillary action, and the antigen fixed on the T line can be competitively combined with the free antigen and the antibody in the sample.
Finally, the invention also relates to a method for immunochromatographic detection, which comprises the following steps:
(1) providing the organic microsphere or the probe or the test paper with long afterglow luminescence;
(2) irradiating the organic microspheres or the probes or the test paper with exciting light; and
(3) stopping irradiation, and reading a light emitting signal.
Compared with similar technology such as CN105929155A which adopts inorganic long afterglow material, the immunochromatography detection method of the invention has more advantages. First, the excitation wavelength is more widely selectable, including the wavelength range of ultraviolet, visible, and near-infrared light. Secondly, the absorption cross section of the long-lasting phosphor microsphere is larger by several orders of magnitude, which enables the time for charging energy by light irradiation to be shorter, such as 2 s-10 s is the most preferable. In addition, the long-afterglow luminescent microspheres have higher long-afterglow luminescent brightness which exceeds the macroscopic brightness level, and the selectable detection equipment is more common. Preferably, the instrument for reading the luminescence signal in the detection is a mobile phone, a luminescence imaging system, a professional long afterglow luminescence detection device, and the like. More preferably, the detection device is a common commercial mobile phone, and is provided with software for reading signals, so that data analysis of signal intensity can be performed on pictures taken by the mobile phone.
FIG. 1 is a schematic structural diagram of a probe containing a long-afterglow luminescent microsphere according to the invention. As can be seen, components A) to C) are adsorbed on the carrier medium microspheres, to which antibodies or aptamers are also coupled.
FIG. 2 is a schematic diagram of the luminescence mechanism of the long afterglow luminescent nano material according to the present invention.
FIG. 3 is a schematic diagram of the immunochromatographic test strip of the present invention, which comprises a PVC base plate 1, wherein a sample pad 2, a binding pad 3, a nitrocellulose membrane 4 and a water absorption pad 5 are sequentially arranged on the base plate 1; the nitrocellulose membrane 4 is also provided with a test line 6 and a quality control line 7 in this order along the direction from the sample pad 2 to the absorbent pad 5, and the direction indicated by the arrow in the figure is the lateral chromatographic direction.
FIG. 4 is a transmission electron microscope image of the long persistence luminescent nanoparticles of example 1.
FIG. 5 shows a bright field (a) of the long-afterglow material taken under the illumination of indoor lighting, and a long-afterglow luminescent picture (b) taken in the dark after the excitation light of 365nm is turned off. The left sample is the long afterglow luminescent nano material of the invention example 1, and the right sample is the inorganic long afterglow SrAl of the comparative example 12O 4:Eu 2+,Dy 3+And (3) nano materials.
FIG. 6 is a standard curve of C-reactive protein (CRP) detection based on the long-afterglow luminescent nano-materials of the embodiment 31 of the invention.
FIG. 7 is a diagram showing the effect of a long-afterglow immunochromatographic strip for detecting C-reactive protein (CRP) using the same mobile phone. The long afterglow signal indicating probes used in the immunochromatographic test strip are different, the left graph (a) is a CRP detection effect graph of the long afterglow luminescent nano material based on the embodiment 31 of the invention, and the right graph (b) is an inorganic long afterglow SrAl based on the comparative embodiment 112O 4:Eu 2+,Dy 3+And (3) a CRP detection effect graph of the nano material.
FIG. 8 is a standard curve for serum amyloid (SAA) detection based on the long persistence luminescent nanomaterial of example 32 of the present invention.
FIG. 9 is a standard curve for Procalcitonin (PCT) detection based on the long-lasting luminescent nanomaterial of embodiment 33 of the present invention.
FIG. 10 is a standard curve for alpha-fetoprotein (AFP) detection based on the long persistence luminescent nanomaterials of example 34 of the present invention.
FIG. 11 is a calibration curve for carcinoembryonic antigen (CEA) detection based on the long persistence luminescent nanomaterial of embodiment 35 of the present invention.
FIG. 12 is a standard curve for Prostate Specific Antigen (PSA) detection based on the long persistence luminescent nanomaterial of embodiment 36 of the present invention.
FIG. 13 is a standard curve of the detection of cardiac troponin (CTn-I) based on the long-lasting luminescent nanomaterial of example 37 of the present invention.
1. Performance test method
In the long persistence luminescence test of the present invention, a wavelength tunable laser (Opolette 355) from the company of Opotek, inc. In certain cases, Light Emitting Diodes (LEDs) are also used as excitation light sources, the power density of the excitation light being kept uniform. The excitation light with specific wavelength irradiates the sample for energy charging, and the irradiation energy charging time is 3 s. And after the energy charging is finished, the laser is turned off, and the light emitting performance is tested. The long afterglow luminescence intensity measurements were carried out using an Edinburgh FS-5 fluorescence spectrometer. The long afterglow luminance was measured using a long afterglow measurement system (OPT-2003) of the beijing obodi photoelectric technology ltd. The invention uses a commercial smart phone or a common digital camera to take a picture and records a bright field and a long afterglow luminous picture.
As used herein, the phrase "visible to the naked eye" is a term used in the art of long persistence luminescent materials and means that the luminescent brightness of the material is greater than or equal to 0.32 mcd.m-2Visible light is typically visible to the naked eye at levels of radiation at and above this brightness. The phrase "emission time" as used herein is a term of art in the field of long persistence luminescent materials and refers to the time that elapses when the emission brightness of the material decays to a level that is visible to the naked eye. The phrase "blue long afterglow luminescence" as used herein is a representation of the long afterglow luminescence color of a material, meaning that there is significant long afterglow luminescence generation in the blue wavelength interval; similarly, the description correspondingly applies to the description of the other colors used herein. In a practical case, there may be an error in the observation result such as a light emission color or a light emission time due to a difference in the observation method or due to an influence of an individual difference.
2. List of raw materials used
3. Preparation of long afterglow luminescent nano material
Example 1
Preparing the long-afterglow luminescent organic microspheres, wherein the content of the carrier medium is 75 percent of the total mass of the four components A) to D). First, a light absorbent PdOEP, a luminescent agent Eu-1 and a photochemical buffer CA-1 are mixed in a dichloromethane solvent, and ultrasonic waves are used for assisting the dissolution of each component. In the solution, the concentration of the light absorbent PdOEP is 0.1mmol L-1The photochemical buffer agent CA-1 has a molar concentration of 3mmol L-1The concentration of the luminescent agent Eu-1 is 10mmol L-1The molar ratio of the light absorbent to the photochemical buffering agent to the luminescent agent is 1:30: 100. To 1mL of the solution, 10mg of liquid paraffin and 20mg of Bovine Serum Albumin (BSA) were added, followed by 10mL of deionized water. Using ultrasound (sonic VC750, sonic)&Materials, Inc) the mixture was pre-emulsified at room temperature for 5 minutes in the dark and dichloromethane was removed using a rotary evaporator. The emulsion was then immediately continued from light for 10 minutes using a high pressure nano homogeniser (FB-110Q, LiTu Mechanical Engineering Co., Ltd.). The emulsion was heated at 90 ℃ for 1 hour in the dark. After the emulsion is cooled to room temperature, the long afterglow luminescent microspheres uniformly dispersed in water are obtained by gradient centrifugation and filtration. The microspheres were dyed with sodium phosphotungstate and the morphology under transmission electron microscopy is shown in fig. 4. Testing the afterglow performance of the prepared long afterglow luminescent microsphere, and preparing the long afterglow luminescent microsphere into 1mg mL -1A concentrated aqueous solution. Firstly, an LED light source with the wavelength of 365nm is used for irradiating for 3s for energy charging, the light source is turned off after the energy charging is finished, and macroscopic red long afterglow luminescence is obtained, and the test results are shown in Table 1.
COMPARATIVE EXAMPLE 1(C1)
Preparing the long-afterglow luminescent inorganic microspheres, wherein the content of the carrier medium is 67 percent based on the total mass of the carrier medium and the inorganic long-afterglow luminescent nanoparticles. In the commercialized inorganic long afterglow material, SrAl2O 4:Eu 2+,Dy 3+The material is a green long-afterglow luminescent material with the highest brightness at present and has very wide application. Commercial SrAl2O 4:Eu 2+,Dy 3+The material is a long afterglow powder obtained by high temperature sintering and then grinding. Obtaining SrAl with the particle size of about 50nm by centrifugal separation2O 4:Eu 2+,Dy 3+Inorganic long persistence nanoparticles. Then, 10mg of the inorganic nanoparticles were modified with 20mg of BSA in an aqueous solution and subjected to a treatment such as ultrasonic emulsification as described in example 1. Finally obtaining the inorganic long-afterglow microsphere coated by BSA, wherein the particle size is about 300 nm. The BSA coated inorganic long-lasting microspheres were prepared in 1mg mL by the method of example 1-1The water solution with the concentration is used for testing the afterglow performance of the microspheres, the result is observed by naked eyes without any afterglow light, and the long afterglow luminous intensity tested by an instrument is shown in table 1.
Examples 2 to 8
The procedure of example 1 was repeated, wherein the molar ratio of the three components, light absorber, photochemical buffer and light emitter, was maintained at 1:30:100, except as shown in Table 1.
Example 9
Preparing the long-afterglow luminescent organic microspheres, wherein the feeding amount of the carrier medium is 50 percent of the total mass of the four components A) to D). Adding a light absorbent PdOEP, a luminescent agent Eu-1 and a photochemical buffer agent CA-1 into 5mL of benzyl alcohol-ethylene glycol-water (v: v: v, 1:8:1) solution, wherein the concentration of the light absorbent PdOEP is 0.1mmol L-1The concentration of the photochemical buffering agent CA-1 is 3mmol L-1The concentration of the luminescent agent Eu-1 is 10mmol L-1The molar ratio of the light absorbent, the photochemical buffering agent and the luminescent agent is 1:30: 100. Each componentAfter ultrasonic dispersion, 50mg of styrene Polymer (PS) microspheres with carboxyl on the surface are added and heated at 110 ℃ for 30 min. Then, the mixture was cooled to room temperature, washed 3 times by centrifugation using ethanol and water, and finally the microspheres were dispersed in water for storage. Testing the afterglow performance of the prepared long afterglow luminescent microsphere, and preparing the long afterglow luminescent microsphere into 1mg mL-1A concentrated aqueous solution. Firstly, excitation light with the wavelength of 540nm is used for irradiation for 3s for energy charging, and the light source is turned off after the energy charging is finished, so that macroscopic red long afterglow luminescence is obtained, and the test results are shown in table 1.
Example 10
Preparing the long-afterglow luminescent organic microspheres, wherein the feeding amount of the carrier medium is 50 percent of the total mass of the four components A) to D). Adding a light absorbent PdOEP, a luminescent agent Eu-1 and a photochemical buffer agent CA-1 into 10mL of mesitylene-ethanol (v: v, 1:1) solution, wherein the concentration of the light absorbent PdOEP is 0.1mmol L-1The concentration of the photochemical buffer agent CA-1 is 3mmol L-1The concentration of the luminous agent Eu-1 is 10mmol L-1The molar ratio of the light absorbent to the photochemical buffering agent to the luminescent agent is 1:30: 100. After the components are dispersed by ultrasonic, 100mg of silicon microspheres with amino groups on the surfaces are added and heated for 2 hours at 80 ℃. Then, the mixture was cooled to room temperature, washed 3 times by centrifugation using ethanol and water, and finally the microspheres were dispersed in water for storage. Testing the afterglow performance of the prepared long afterglow luminescent microsphere, and preparing the long afterglow luminescent microsphere into 1mg mL-1A concentrated aqueous solution. Firstly, excitation light with the wavelength of 540nm is used for irradiation for 3s for energy charging, and the light source is turned off after the energy charging is finished, so that macroscopic red long afterglow luminescence is obtained, and the test results are shown in table 1.
Examples 11 to 13
The procedure of example 1 was repeated, wherein the molar ratio of the three components, light absorber, photochemical buffer and light emitter, was maintained at 1:30:100, except as shown in Table 1.
COMPARATIVE EXAMPLES 2 to 3(C2 AND C3)
The procedure of example 1 was repeated, wherein the molar ratio of the three components, light absorber, photochemical buffer and light emitter, was maintained at 1:30:100, except as shown in Table 1.
COMPARATIVE EXAMPLE 4(C4)
The long afterglow microsphere is prepared by taking NCBS as a light absorbing agent, PFVA as a luminescent agent and DO as a photochemical buffering agent. The components are mixed in a dichloromethane solvent, ultrasonic waves are used for assisting the dissolution of the components, and finally, a uniform and transparent solution is formed. In this solution, the concentration of the light absorbent NCBS was 0.1mmol L-1The photochemical buffer agent DO has a molar concentration of 2mmol L-1The concentration of the luminophore PFVA was 10mg mL-1. Subsequently, 1mL of the above solution was taken, and 10mg of liquid paraffin and 20mg of Bovine Serum Albumin (BSA) were added thereto, followed by 10mL of deionized water. Use of ultrasound (Sonics VC750, Sonics)&Materials, Inc) the mixture was pre-emulsified at room temperature for 5 minutes in the dark and dichloromethane was removed using a rotary evaporator. The emulsion was then immediately continued from light for 10 minutes using a high pressure nano homogeniser (FB-110Q, LiTu Mechanical Engineering Co., Ltd.). The emulsion was heated at 90 ℃ for 1 hour in the dark. After the emulsion is cooled to room temperature, the long afterglow microsphere which is evenly dispersed in water is obtained by gradient centrifugation and filtration. The long afterglow luminescent microsphere prepared by the method of the example 1 is subjected to afterglow performance test, and the long afterglow luminescent microsphere is prepared into 1mg mL -1A concentrated aqueous solution. Firstly, excitation light with the wavelength of 808nm is used for energy charging for 3s, the light source is turned off after the energy charging is finished, and consequently, no afterglow light is observed by naked eyes, and the long afterglow luminous intensity tested by means of an instrument is shown in table 1.
COMPARATIVE EXAMPLE 5(C5)
The operation of comparative example 6 was repeated except for the differences shown in Table 1.
COMPARATIVE EXAMPLE 6(C6)
The long-afterglow microsphere is prepared by taking PtTPBP as a light absorbent, Eu-1 as a luminescent agent and CA-1 as a photochemical buffering agent. The components are first dissolved in 2mL Tetrahydrofuran (THF) with a concentration of 0.1mmol L of the light absorber PdOEP-1The concentration of the photochemical buffer agent CA-1 is 3mmol L-1The concentration of the luminescent agent Eu-1 is10mmol L -1The molar ratio of the light absorbent to the photochemical buffering agent to the luminescent agent is 1:30: 100. To the above solution was added 20mg of F127 and dissolved with stirring, then tetrahydrofuran was removed, and the obtained composition was dispersed in 2mL of water using ultrasonic waves, followed by centrifugation and filtration to obtain long-afterglow microspheres uniformly dispersed in water. The long afterglow luminescent microsphere prepared by the method of the example 1 is subjected to afterglow performance test, and the long afterglow luminescent microsphere is prepared into 1mg mL-1A concentrated aqueous solution. Firstly, excitation light with the wavelength of 635nm is used for energy charging for 3s, the light source is turned off after the energy charging is finished, no long afterglow luminescence which is obviously visible to naked eyes is observed, and the test results are shown in table 1.
TABLE 1
Example 14
Mixing a light absorbent PdPpc, a luminescent agent Eu-2 and a photochemical buffering agent CA-1 in a dichloromethane solvent, and using ultrasonic waves to assist the dissolution of all components to finally form a uniform and transparent solution. In this solution, the photochemical buffer agent CA-1 has a molarity of 2mmol L-1The concentration of the luminescent agent Eu-2 is 5mmol L-1The concentration of the light absorbent PdPdpc is 50 mu mol L-1. Subsequently, 1mL of the above solution was taken, and 10mg of liquid paraffin and 20mg of Bovine Serum Albumin (BSA) were added thereto, followed by 10mL of deionized water. Using ultrasound (sonic VC750, sonic)&Materials, Inc) the mixture was pre-emulsified at room temperature for 5 minutes in the dark and dichloromethane was removed using a rotary evaporator. The emulsion was then immediately continued from light for 10 minutes using a high pressure nano homogeniser (FB-110Q, LiTu Mechanical Engineering Co., Ltd.). Subjecting the emulsion to a temperature of 90 deg.CLight heating for 1 hour. After the emulsion is cooled to room temperature, the long afterglow microsphere which is evenly dispersed in water is obtained by gradient centrifugation and filtration. Testing the afterglow performance of the prepared long afterglow luminescent microsphere, and preparing the long afterglow luminescent microsphere into 1mg mL-1A concentrated aqueous solution. First, the light source was turned off after the charging was completed by irradiating the laser beam with the excitation light having a wavelength of 730nm for 3 seconds, and the test results are shown in Table 2.
Examples 15 to 19
The procedure of example 14 was repeated except that the concentration of the luminescent agent Eu-2 is 5mmol L as shown in Table 2-1。
COMPARATIVE EXAMPLES 7 to 8(C7 AND C8)
The procedure of example 14 was repeated except that the difference shown in Table 2 was that the concentration of the luminescent agent Eu-2 was 5mmol L-1。
TABLE 2
Example 20
Mixing a light absorbing agent PdPpc, a luminescent agent Eu-1 and a photochemical buffering agent CA-1 in dichloromethane, and using ultrasonic waves to assist the dissolution of all components to finally form a uniform and transparent solution. In the solution, the molar ratio of the light absorbent PdPpc, the photochemical buffer agent CA-1 and the luminescent agent Eu-1 is 1:300: 3000. Then, the dichloromethane solvent was removed to obtain an oily mixture of three components A)/B)/C). 50mg of the three-component mixture is weighed and added into a component D) containing 30mg of liquid paraffin and 20mg of bovine serum albumin, wherein the component D) accounts for 50 percent by weight. Using ultrasound (sonic VC750, sonic)&Materials, Inc) pre-emulsify the aqueous solution of the mixture at room temperature for 5 minutes in the dark, and then immediately continue to emulsify in the dark for 10 minutes using a high pressure nano homogenizer (FB-110Q, liu Mechanical equipment Engineering co., Ltd). The emulsion was heated at 90 ℃ for 1 hour in the dark. After the emulsion had cooled to room temperature, it was centrifuged and filtered by gradient The long-afterglow microsphere which is uniformly dispersed in water is obtained. Testing the afterglow performance of the prepared long afterglow luminescent microsphere, and preparing the long afterglow luminescent microsphere into 1mg mL-1A concentrated aqueous solution. First, the light source was turned off after the charging was completed by irradiating the laser beam with 540nm wavelength for 3 seconds, and the test results are shown in table 3.
Examples 21 to 23
The operation of example 20 was repeated except for the weight ratio of the D) component in the nanomaterial (as shown in Table 3). The test results are shown in table 3.
COMPARATIVE EXAMPLES 9 to 10(C9 AND C10)
The operation of example 20 was repeated except for the weight ratio of the D) component in the nanomaterial (as shown in Table 3). The test results are shown in table 3.
TABLE 3
Example 24
Taking 80nm styrene Polymer (PS) microspheres with carboxyl, centrifuging, removing a surfactant in the synthesis process, then re-dissolving 1g of PS microsphere solid into 100mL of ultrapure water, and performing ultrasonic treatment to form a dispersed phase. Then, 1mL each of 2% sodium dodecylbenzenesulfonate and 1% ethylenediamine polyoxyethylene polyoxypropylene block polyether was added to the PS microsphere aqueous solution, and the mixture was stirred. Taking the components A), B) and C) as shown in the table 4, dispersing the components in 10mL tetrahydrofuran solution to form a dispersed phase, wherein the concentrations of the components A), B) and C) are respectively 0.1mmol L -1、2mmol L -1And 10mmol L-1. After the solution formulation was complete, the organic phase was added rapidly to the aqueous phase, then gradually warmed to 50 ℃ and stirred continuously for 10 h. And centrifuging the obtained long-afterglow PS microspheres with the particle size of 80nm, removing redundant dye, cleaning twice by using ultrapure water and ethanol, storing in the ultrapure water, and keeping away from light at normal temperature for standby.
Examples 25 to 28
The procedure of example 24 was repeated except for the particle size of the styrene Polymer (PS) microspheres having carboxyl groups as a nano-carrier medium (as shown in table 4). The test results are shown in table 4.
TABLE 4
Example 29
Coupling of alpha-fetoprotein (AFP) antibody AFP-Ab through fluorescent long-afterglow microspheres1Preparing a probe:
1) taking 100mg of the long-afterglow luminescent microspheres prepared according to the embodiment 26, centrifuging, redissolving the microspheres into 18mL of BBS buffer solution with the pH value of 7.4, and fully and uniformly dispersing the microspheres by ultrasonic waves; 2) 2mg of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and 2mg of N-hydroxysuccinimide sulfonic acid sodium salt (NHSS) were added thereto, respectively, and reacted at room temperature for 2 hours; 3) after the reaction was completed, the reaction mixture was centrifuged and washed, redissolved in 10mL of BBS buffer solution having pH 7.4, and 10mg of AFP-Ab was added thereto1Reacting the monoclonal antibody at room temperature for 4 hours; 4) after the reaction is finished, centrifugally washing, redissolving into 10mL of BBS buffer solution with the pH value of 7.4, adding 100mg of BSA into the BBS buffer solution, and reacting for 2 hours at room temperature; 5) after the reaction, the reaction mixture was washed by centrifugation, redissolved in 10mL of BBS buffer solution having a pH of 7.4, and stored at 4 ℃ until use.
Example 30
Preparing a probe by coupling the long afterglow microsphere with a Prostate Specific Antigen (PSA) aptamer:
1) 10mg of the carboxyl-containing long-lasting microspheres prepared according to example 26 were centrifuged, redissolved in 1.8mL of BBS buffer (pH 7.4), and sufficiently sonicated to disperse them uniformly; 2) 0.6mg of EDC and 0.2mg of NHSS were added thereto, respectively, and the mixture was reacted with shaking at room temperature for 2 hours; 3) after the reaction was completed, the reaction mixture was washed by centrifugation, redissolved in 2mL of BBS buffer, and 20. mu.L of a solution containing 2. mu. mol mL of BBS buffer was added thereto-1The PSA aptamer of (9), having the sequence of (NH)2-ATTAAAGCTCGCCATCAAATAGCTGC), chamberReacting for 4 hours at room temperature; 4) after the reaction is finished, centrifugally washing, redissolving the mixture into 2mL of BBS buffer solution, adding 10mg of BSA into the BBS buffer solution, and reacting for 2 hours at room temperature; 5) after the reaction, the reaction mixture was washed 2 times by centrifugation, redissolved in 4mL of BBS buffer (pH 7.4), and stored at 4 ℃ for further use.
Example 31
Preparation of lateral chromatography immune test strip containing long-afterglow luminescent microspheres and application of lateral chromatography immune test strip in C-reactive protein (CRP) detection
(1) Preparation of an immunochromatographic test strip for detecting C-reactive protein (CRP):
1) coupling of Long-persistence microspheres to CRP-Ab in example 1 as described below1: using PEG with carboxyl at two ends, firstly activating the carboxyl at two ends, then reacting and connecting one end with amino on the BSA nanosphere, and connecting the other end with CRP-Ab 1The amino groups are connected in a reaction way. Wherein 10mg of CRP-Ab is added to 100mg1Monoclonal antibodies of type (I). After the reaction, the reaction mixture was centrifuged and washed, redissolved in 10mL of BBS buffer solution with pH 7.4, and stored at 4 ℃ until use.
2) Preparing an NC membrane of the CRP immunochromatographic test strip: CRP-Ab was treated with PBS buffer (1% BSA, 1% sucrose, 50mM NaCl and 0.5% TWEEN 20), respectively2The monoclonal antibody and donkey anti-mouse IgG are respectively added in a dosage of 1mg mL-1And 1mg mL-1And, at 8mm intervals, scratched on a nitrocellulose membrane with a streaking machine, and dried overnight at 37 ℃.
3) Preparing a CRP immunochromatographic test strip sample pad: taking the prepared fluorescent probe in the step 1), centrifuging, and redissolving the fluorescent probe into 20mg mL by using a film spraying buffer solution-1The fluorescent probe solution was sucked back into the instrument by a membrane spraying instrument at 1.2. mu.L cm-1The fluorescent probe was sprayed onto the glass fiber and baked at 37 ℃ overnight.
4) Assembling the CRP immunochromatographic test strip: CRP-Ab is sequentially and alternately stuck on a white PVC bottom plate by 3mm1Glass fiber of fluorescent microsphere of monoclonal antibody type, scratched with CRP-Ab2The NC membrane of the T line of (1) and the C line of donkey anti-mouse IgG,and finally, attaching absorbent paper. And then cutting the assembled chromatography plate into test strips with the width of 3.8mm by a high-speed cutting machine, and fixing the test strips by using an upper plastic clamping shell and a lower plastic clamping shell which are matched to obtain the immunochromatographic test strip.
(2) Establishment of CRP standard curve in sample:
1) the CRP antigen stock solution is diluted into whole blood CRP antigen solutions with different concentrations of 0 mug mL respectively by using the samples-1、5μg mL -1、20μg mL -1、40μg mL -1、160μg mL -1And 320. mu.g mL-1。
2) mu.L of the sample CRP antigen solution was added to 99. mu.L of PBS buffer (containing 1% BSA, 0.1% SDS, and 0.1% B66) and mixed well.
3) And adding 100 mu L of the mixed solution which is uniformly mixed into a sample adding hole of the immunochromatographic test strip, wherein the liquid can sequentially pass through a sample area, a detection area and a water absorption area through capillary action. When the antigen solution is detected in the sample, the antigen is firstly combined with the long afterglow luminescent probe in the sample area to form immune complex, and then the immune complex and the CRP-Ab are electrophoresed to a test line (T line) along with the liquid2A sandwich immune complex is formed, and the redundant long afterglow luminescent probe swims to a control line (C line) to be combined with the donkey anti-mouse secondary antibody. And when no antigen exists in the detection sample, the long afterglow luminescent probe is driven to directly swim to the C line to be combined with the donkey anti-rat secondary antibody.
4) After the reaction is carried out for 5 minutes, the immunochromatographic test strip is detected by using a long-afterglow luminescence detector. The long afterglow luminous intensity of the T line and the C line is measured, the peak areas are integrated, the ratio of the peak areas is calculated, and a standard curve is established by the logarithm of the ratio and the antigen concentration (figure 6). The long afterglow luminescence detector is a daily-used commercial smart phone, is provided with signal reading software, and can perform signal intensity data analysis on pictures shot by the mobile phone.
(3) Immunochromatography detection of CRP in a sample:
long persistence luminescent microspheres comprising the invention prepared by excitation with excitation light only prior to readingThe exciting light is in a closed state in the subsequent reading process, the method eliminates the interference of background fluorescence signals, and can realize high-sensitivity quantitative detection of the object to be detected. In the detection of CRP samples, the immunochromatographic test strip (figure 7 left) based on the long-afterglow luminescent microspheres of the invention has the detection sensitivity which is improved by more than 100 times compared with the detection system (figure 7 right) based on inorganic long afterglow, but has no obvious change on the treatment requirements of the detection samples, and the part of the detection time only needs 3s on the excitation time. According to the detection result of the long afterglow luminescence immunochromatographic test strip, the sample contains 100ng mL-1Is far below normal physiological levels.
COMPARATIVE EXAMPLE 11(C11)
The operation of example 31 was repeated except that: in the first step, the inorganic long-lasting microspheres of comparative example 1 were used to couple CRP-Ab1. The prepared inorganic long-afterglow nano immunochromatographic test strip has weak long-afterglow luminescent signals, can not be seen by naked eyes and can not be shot by a mobile phone, as shown in the right diagram in fig. 7.
Examples 32 to 37
The procedure of example 31 was repeated to obtain an antigen detection standard curve based on the long-lasting afterglow lateral chromatographic immunoassay strip, except that the target antigens were replaced with: SAA (example 32, fig. 8), PCT (example 33, fig. 9), AFP (example 34, fig. 10), CEA (example 35, fig. 11), PSA (example 36, fig. 12), CTn-I (example 37, fig. 13).
Claims (27)
- A long persistence luminescent organic microsphere comprisingA) At least one light-absorbing agent,B) at least one luminescent agent which is a monomeric, non-polymeric compound and has a molecular weight of less than 10000g mol-1，C) At least one photochemical buffer agent of formula (I),
wherein the content of the first and second substances,g and T are heteroatoms selected from O, S, Se and N;R 1' and R2' and R4' to R8' are each independently selected from H, hydroxyl, carboxyl, amino, mercapto, ester, nitro, sulfonic, halogen, amide, or alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, aryl, aralkyl, heteroaryl or heteroaralkyl having N, O or S, or combinations thereof, having 1 to 50, preferably 1 to 24, carbon atoms, such as 2 to 14, wherein the aryl, aralkyl, heteroaryl or heteroaralkyl optionally has one or more substituents L; andL is selected from hydroxyl, carboxyl, amino, thiol, ester, nitro, sulfonic, halogen, amide, or alkyl, alkenyl, alkynyl, alkoxy, and alkylamino groups having 1 to 50, preferably 1 to 24, such as 2 to 14, or 6 to 12 carbon atoms, or combinations thereof; andR 3' is an electron withdrawing group or an aryl group comprising an electron withdrawing group, preferably selected from nitro, halogen, haloalkyl, sulfonic acid, cyano, acyl, carboxyl, and/or combinations thereof; andD) a support medium for adsorbing components A) to C);wherein the light absorber and the light emitter are structurally different compounds and the content of the carrier medium is from 30% to 99%, more preferably from 35% to 95% and most preferably from 40% to 90% based on the total mass of the four components A) to D). - The long persistence luminescent organic microsphere of claim 1, wherein the ring portion isIs selected from
More preferably G and T are selected from S and O, most preferably one of G and T is S and the other is O.
- The long-lasting luminescent organic microsphere according to claim 1 or 2, characterized in that the group R1' and R2' and R4' to R8' are each independently selected from alkyl, alkoxy, alkylamino or aryl groups having 1 to 18, preferably 1 to 12, more preferably 1 to 16 carbon atoms, or combinations thereof, wherein said aryl groups may be substituted or unsubstituted with one or more groups L and are preferably phenyl substituted or unsubstituted with one or more groups L.
- A long persistence luminescent organic microsphere according to any preceding claim, wherein L is selected from hydroxyl, sulfonic acid group, halogen, nitro group, straight or branched alkyl group having 1 to 12, more preferably 1 to 6 carbon atoms, alkoxy group, alkylamino group, amino group, or their combination;more preferably selected from halogen, straight or branched alkyl, alkoxy, alkylamino having 1 to 12, more preferably 1 to 6 carbon atoms, or combinations thereof.
- Long afterglow luminescent organic microsphere according to any of the preceding claims, wherein the group R1' and R2' and R4' to R8' is selected from methoxy, ethoxy, dimethylamino, diethylamino, dibutylamino, methyl, ethyl, propyl, butyl, tert-butyl, or combinations thereof.
- Long persistent light-emitting organic microsphere according to any one of the preceding claims, characterized in that the electron withdrawing groups are selected from nitro, cyano, halogen, haloalkyl and/or combinations thereof and the aryl group comprising electron withdrawing groups is selected from aryl groups having one or more substituents on the ring selected from nitro, cyano, halogen and/or haloalkyl, preferably phenyl, wherein the halogen and haloalkyl are preferably fluorine and fluoroalkyl.
- Long persistence luminescent organic microsphere according to anyone of the preceding claims, characterized in that the photochemical buffering agent is selected from one or more of the following compounds:
- a long persistent light-emitting organic microsphere according to any one of the preceding claims, wherein the carrier medium is selected from one or more of a styrene polymer microsphere, a protein nanomedia and a silicon microsphere, more preferably a protein nanomedia and/or a styrene polymer microsphere; also preferably, the surface of the support matrix contains amino, carboxyl and/or aldehyde groups.
- A long persistence luminescent organic microsphere according to claim 8, wherein the protein used to form the protein nanomedia is selected from one or more of bovine serum albumin, human serum albumin, silk fibroin, casein and more preferably bovine serum albumin.
- Long persistent light-emitting organic microsphere according to any of the preceding claims, characterized in that it has a particle size in the range of 5 nm-1000 nm, more preferably 50 nm-800 nm, most preferably 100 nm-500 nm.
- A long persistence luminescent organic microsphere according to any of the preceding claims, wherein the molar ratio of light absorber to luminescent agent is in the range of 1:2 to 1:10000, preferably 1:10 to 1:8000 or 1:50 to 1:6000, more preferably 1:100 to 1:4000 or 1:200 to 1: 2000.
- A long persistence luminescent organic microsphere according to anyone of the preceding claims, wherein the photochemical buffering agent is present in an amount of 0.1% to 80%, preferably 0.3% to 60%, more preferably 0.5% to 40%, most preferably 1% to 20% by mass of the total mass of components a) to C).
- Long afterglow luminescent organic microsphere according to any of the preceding claims, wherein the long afterglow luminescent organic nanoparticle consists of components a) to D).
- A long-lasting luminescent organic microsphere according to any one of the preceding claims, wherein the luminescent agent is selected from iridium complexes, rare earth complexes, acenes, BODIPY, and derivatives and copolymers thereof.
- A probe comprising the long persistent luminescent organic microsphere according to any one of claims 1 to 14 and an antibody or aptamer loaded or coupled thereon.
- A probe according to claim 15, wherein the antibody or aptamer is present in the probe in an amount of preferably 1% to 20%, more preferably 2% to 15%, most preferably 5% to 12% by mass of the entire probe.
- The probe of claim 15 or 16, wherein the antibody or aptamer is selected from the group consisting of a C-reactive protein (CRP) antibody, a serum amyloid protein (SAA) antibody, a Procalcitonin (PCT) antibody, an alpha-fetoprotein (AFP) antibody, a carcinoembryonic antigen (CEA) antibody, a Prostate Specific Antigen (PSA) antibody, a cardiac troponin (CTn-I) antibody, and/or an oligonucleotide fragment.
- A method of preparing long afterglow luminescent organic microspheres according to any one of claims 1 to 14 comprising the steps of:(1) providing components A) to C); and(2) the components A) to C) are dispersed and adsorbed onto the support medium component D) in a dispersion or solution.
- The process according to claim 18, characterized in that components a) to C) are dispersed or dissolved using one or more solvents selected from liquid paraffin, a mixture of phenethyl alcohol-ethylene glycol and water, a mixture of mesitylene and ethanol, tetrahydrofuran and dichloromethane.
- Method for preparing a probe according to claim 15, wherein an antibody or aptamer is adsorbed or modified on a long-lasting luminescent organic microsphere according to any one of claims 1 to 14.
- The method according to claim 20, wherein comprising bioconjugating said long persistent luminescent organic microsphere with an antibody or aptamer through a functional reactive group such as carboxyl, amino, aldehyde group.
- A strip for immunochromatographic detection comprising a long-lasting luminescent organic microsphere according to any one of claims 1 to 14 or a probe according to any one of claims 15 to 17.
- The test paper of claim 22, which comprises a sample pad, a bonding pad, a test line and a quality control line, wherein the long afterglow luminescent organic microsphere or the probe is arranged on the bonding pad.
- A method of immunochromatographic detection comprising the steps of:(1) providing a long afterglow luminescent organic microsphere according to any one of claims 1 to 14, a probe according to any one of claims 15 to 17 or a test paper according to any one of claims 20 to 21;(2) irradiating the organic microspheres or the probes or the test paper with exciting light; and(3) the irradiation is stopped and the light emission signal is read.
- The detection method according to claim 24, wherein the tunable interval of the excitation wavelength is 300nm to 1000 nm.
- The detection method according to claim 24, wherein the light irradiation time is 2s to 10 s.
- The detection method according to claim 24, wherein the instrument for reading the luminescence signal is selected from a mobile phone, a luminescence imaging system and/or a professional long persistence luminescence detection device, more preferably a mobile phone.
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| CN114437711B (en) * | 2022-01-07 | 2023-09-29 | 南京航空航天大学 | Long glow powder microshell material for traffic facility driving safety prompt and preparation method thereof |
| CN116482084A (en) * | 2023-02-13 | 2023-07-25 | 上海索昕生物科技有限公司 | Photosensitive microsphere for photoexcitation chemiluminescence detection |
| CN116144355A (en) * | 2023-03-09 | 2023-05-23 | 郑州大学 | Ultra-long-time near-infrared water-soluble afterglow luminous carbon dot and preparation method and application thereof |
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|---|---|---|---|---|
| US6284156B1 (en) * | 1998-11-19 | 2001-09-04 | Kabushiki Kaisha Ohara | Long-lasting phosphor, powdered long-lasting phosphor and method for manufacturing the powdered long-lasting phosphor |
| WO2008155813A1 (en) * | 2007-06-19 | 2008-12-24 | Itakura, Masako | Resin molding |
| CN106833622A (en) * | 2017-01-10 | 2017-06-13 | 南京工业大学 | A kind of pure organic long-afterglow material of excited by visible light and preparation method and application |
| CN108956556A (en) * | 2018-05-18 | 2018-12-07 | 复旦大学 | A kind of luminescence probe and time-resolved fluorescence detection system |
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| US6284156B1 (en) * | 1998-11-19 | 2001-09-04 | Kabushiki Kaisha Ohara | Long-lasting phosphor, powdered long-lasting phosphor and method for manufacturing the powdered long-lasting phosphor |
| WO2008155813A1 (en) * | 2007-06-19 | 2008-12-24 | Itakura, Masako | Resin molding |
| CN106833622A (en) * | 2017-01-10 | 2017-06-13 | 南京工业大学 | A kind of pure organic long-afterglow material of excited by visible light and preparation method and application |
| CN108956556A (en) * | 2018-05-18 | 2018-12-07 | 复旦大学 | A kind of luminescence probe and time-resolved fluorescence detection system |
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